The retina is supplied with oxygen and nutrients by two vascular systems, one within the retina itself (central retinal artery) and one in the choroid (posterior ciliary artery). Interruption or impairment of either system leads to degeneration of the retina and ultimately to loss of vision. There are many causes that effect retinal circulation and nutrient supply. Included among diseases and conditions are retinitis pigmentosa, diabetic retinopathy, sickle cell retinopathy, hypertensive and atheroscelerotic vascular diseases, retinal vein occlusion, maculopathy, and glaucoma (LaVaio et al., (1985); U.S. Department of Health and Human Services, (1983)). By providing for enhanced blood flow or nutrient supply to the retina, particularly early in the course of the above indicated diseases, prevention or slowing of vision loss may be achieved. Any drug, given systemically or locally to the eye, that is directed toward a disease symptom but results in a decrease in ocular circulation as a side effect, will normally enhance the visual deterioration, rather than improve it.
Glaucoma serves as an illustration of the problem, where glaucoma is treated by decreasing intraocular pressure (IOP) in order to improve optic nerve, choroidal and retinal circulation. It is found that some patients show retinal degeneration with normal IOP (low tension glaucoma), while others have abnormally increased IOPs with no visual disturbances. This may suggest that the correlation between IOP and retinal circulation is tenuous. A drug may lower IOP and concommitantly decrease retinal and choroidal blood flow (RCBF), leading to the false conclusion that the glaucoma is under control, while in fact retinal damage continues. It is therefore of substantial interest o find drugs which increase ocular circulation as their mechanism with the resulting IOP decrease.